Meanwhile, the efficacy of cancer immunotherapy in NSCLC is hampered by intra-tumor heterogeneity for neoantigens, neoantigen loss, immunosuppressive TME secondary to tumor aneuploidy, and immune checkpoints such as PD-L1 and TIM-3 (Anichini et al. 2018; Anichini et al. 2020; Koyama et al. 2016; Rosenthal et al. 2019). The gene discussed is HAVCR2; the disease is cancer.